Disease type and/or condition determination method and apparatus and drug screening method and apparatus

ABSTRACT

The object of the present invention is to provide a disease type and/or condition determination method and apparatus that enables rapid and reliable determination by spectral analysis of the energy state of cells or drugs, and a drug screening method and apparatus that enables efficient screening of a target drug. In order to achieve this object, for example, the disease type and/or condition determination method according to the present invention determines disease type and condition by measuring the absorption spectrum in, for example, the infrared region for cells obtained from a specimen, and determining whether or not a coinciding absorption spectrum exists for those measurement results by using as indices at least two infrared absorption spectra.

[0001] This application is a continuation of PCT/JP00/01552 filed onMar. 14, 2000.

TECHNICAL FIELD

[0002] The present invention relates to a disease type and/or conditiondetermination method and apparatus, which enables a fast and reliablediagnosis to be made by identifying the specificity of cells and soforth based on physical aspects, and a drug screening method andapparatus, which enables efficient screening of a target drug.

BACKGROUND ART

[0003] There has been little research in the past that discusses, forexample, the “definition of cancer cells” based on the “absolutespecificity” of cancer cells relative to normal cells. Even with respectto carcinogenic genes and other cancer-related genes that have attractedparticular attention in recent years, although there are currentlyreports stating that these are common to certain partial cell groups ofcancer cells or are present in normal cells as well, these are merely adiscussion relating to the “partial or relative specificity” of cancercells. In other words, research thus far has consisted primarily of thatwhich treats the cell membrane, enzymes and genes, etc. of cancer cellsindependently, attempts to indicate “absolute specificity” within them,and is biased towards a substance-oriented approach that includesidentification of form and structural substances, elucidation of genestructure and so forth.

[0004] However, since there are vast numbers of atoms and molecules thatcompose cells, attempting to structurally define “what is meant bycancer cells” by sorting all of these vast numbers of substances andtheir forms, etc. into normal cells and cancer cells is considered to benearly impossible. Consequently, in the case of research methods thusfar that have employed a substance-oriented approach, it was difficultto identify what cancer cells mean and adequate results have yet to beobtained.

[0005] Therefore, as was previously disclosed in the prior applicationsof Japanese Unexamined Patent Publication No. Hei 9-285286, JapaneseUnexamined Patent Publication No. Hei 9-285296, Japanese UnexaminedPatent Publication No. Hei 9-286739 and Japanese Unexamined PatentPublication No. Hei 9-286740, the inventor of the present invention hasproposed a method for clarifying the “absolute specificity” ofbioactivity (organic substances such as cells, or organic bodies in theform of aggregates of those organic substances) based on physicalaspects.

[0006] This method employs thermodynamic and statistical mechanicalmethods that perceives each cell in the form of a macroscopic system,and indicates the “absolute specificity” of its bioactivity by focusingon the energy state of that system. Namely, this method entraps thebiochemical mechanism of bioactivity within a black box, identifies theatoms and molecules that serve as the constituent elements of cells andso forth by spectral analysis that includes their quantum states, andthen controls their bioactivity. More specifically, this involves, forexample, detecting the characteristic spectrum of cancer cells and thenplanning and designing an anti-cancer agent having a spectrum thatinteracts with the resonance of that characteristic spectrum.

[0007] However, in the determination of the type of a disease and itscondition, a method is desired that allows rapid evaluation of conditionand so forth based on viable cells sampled from a specimen. In addition,in the development of a drug and so forth, a screening method isrequired that is able to efficiently screen for an organism or substancehaving the target effect or ability among a large population.

[0008] The methods of the inventions of the prior applicationspreviously mentioned made it possible to rapidly perform determinationof the type and condition of a disease or selection of a drug by anextremely simple method in the form of spectral analysis. However, theaccuracy of that determination was not always adequate, and there isstill a strong desire for the realization of a more efficient screeningmethod.

[0009] In consideration of the above points, the object of the presentinvention is to provide a disease type and/or condition determinationmethod and apparatus that enable rapid and accurate evaluation, alongwith a drug screening method and apparatus that enables more efficientscreening of a target drug, by performing spectral analysis of theenergy state of cells and drugs and processing those results using aplurality of spectra as indices.

DISCLOSURE OF THE INVENTION

[0010] In order to achieve the above object, the disease type and/orcondition determination method according to the present inventiondetermines the type and/or condition of a disease by analyzing theabsorption or emission spectrum in a specific region of cells obtainedfrom a specimen, and using the appearance of spectra corresponding to atleast two wave numbers within the above specific region as indices inaccordance with the results of the spectral analysis.

[0011] In such a method, in addition to being able to determine the typeand/or condition of a disease by a simple method in the form ofperforming spectral analysis of cells obtained from a specimen, byevaluating and processing the results of spectral analysis by using theappearance of spectra corresponding to at least two wave numbers in aspecific wavelength region as indices, determination of disease type andso forth can be performed more reliably.

[0012] With respect to the above method for determining disease typeand/or condition, the above specific region should include the infraredregion (and preferably any part or the entire range of 10.0 to 13157.9cm⁻¹). In addition, this method is able to determine whether or not thespecimen is cancer, and in this case, one of the wave numbers of thespectrum used as an index should be 1261 cm⁻¹ (and preferably 1261.4cm⁻¹). Moreover, it is also possible to determine whether or not a cellhas specific bacteria, and drug resistance bacteria are a specificexample of the above specific bacteria. In addition, it is also possibleto determine whether or not a cell is infected by a specific virus.

[0013] In addition, the apparatus for diagnosing disease type and/orcondition according to the present invention is composed of spectralanalysis means that analyzes the absorption spectrum or emissionspectrum in a specific region of cells obtained from a specimen, anddiagnostic means that diagnoses disease type and/or condition by usingthe appearance of spectra corresponding to at least two wave numberswithin the above specific region as indices in accordance with theresults of spectral analysis obtained with the spectral analysis means.

[0014] The drug screening method according to the present inventionperforms screening of a target drug by analyzing the absorption spectrumor emission spectrum of the target drug in a specific region using theappearance of spectra corresponding to at least two wave numbers withinthe specific region as indices in accordance with the results of thespectral analysis.

[0015] According to the drug screening method, in addition to enablingrapid screening by using a simple method in the form of spectralanalysis of a target drug, by performing screening by using theappearance of spectra corresponding to at least two wave numbers withina specific region as indices, a drug having the desired effect andcapability can be more reliably extracted.

[0016] In the above drug screening method, the above specific regionshould include the infrared region (and preferably any part or theentire range of 10.0 to 13157.9 cm⁻¹). In addition, screening can beperformed using an anti-cancer agent for the target drug, and in thiscase, one of the wave numbers of the spectrum used as an index should be1261 cm⁻¹ or 1163 cm⁻¹ (and preferably 1261.4 cm⁻¹ or 1163.1 cm⁻¹).Moreover, it is also possible for the target drug to be an antibiotic,and a specific example of an antibiotic is that which is effectiveagainst drug resistance bacteria. In addition, the target drug can alsobe an anti-viral agent.

[0017] The drug screening apparatus according to the present inventionis composed of spectral analysis means that analyzes the absorption oremission spectrum in a specific region of a target drug, and screeningmeans that screens the above target drug by using the appearance ofspectra corresponding to at least two wave numbers in the above specificregion as indices in accordance with the results of spectral analysisobtained with the said spectral analysis means.

BRIEF DESCRIPTION OF THE DRAWINGS

[0018]FIG. 1 is a diagram showing a three-state maser model forexplaining the fundamental items of the present invention.

[0019]FIG. 2 shows graphs illustrating the results of performingspectral analysis using cultured cells derived from ascitic liver canceras a sample.

[0020]FIG. 3 shows graphs illustrating the results of performingspectral analysis using cultured cells derived from mice breast canceras a sample.

[0021]FIG. 4 shows graphs illustrating the results of performingspectral analysis using cultured cells derived from mouse malignantmelanoma as a sample.

[0022]FIG. 5 shows graphs illustrating the results of performingspectral analysis using cultured cells derived from human stomach canceras a sample.

[0023]FIG. 6 shows graphs illustrating the results of performingspectral analysis using cultured cells derived from human glioblastomaas a sample.

[0024]FIG. 7 shows graphs illustrating the results of performingspectral analysis using cancer cells extracted from a breast cancerpatient as a sample.

[0025]FIG. 8 is a diagram providing a systematic representation of thepeak wave numbers of the infrared absorption spectra of various cancercells.

[0026]FIG. 9 shows graphs illustrating changes in energy states causedby destruction of the cell membrane of cancer cells.

[0027]FIG. 10 shows graphs illustrating changes in energy states causedby heating cancer cells.

[0028]FIG. 11 shows graphs illustrating the results of performingspectral analysis using normal rat brain (white matter) cells as asample.

[0029]FIG. 12 shows graphs illustrating the results of performingspectral analysis using normal rat liver cells as a sample.

[0030]FIG. 13 shows graphs illustrating the results of performingspectral analysis using normal mouse mammary gland cells as a sample.

[0031]FIG. 14 shows graphs illustrating the results of performingspectral analysis using normal human bone marrow cells as a sample.

[0032]FIG. 15 is a diagram providing a systematic representation of thepeak wave numbers of the infrared absorption spectra of normal cells.

[0033]FIG. 16 shows graphs illustrating the results of performingspectral analysis using cisplatin as a sample.

[0034]FIG. 17 shows graphs illustrating the results of performingspectral analysis using carboplatin as a sample.

[0035]FIG. 18 shows graphs illustrating the results of performingspectral analysis using doxorubicin hydrochloride (Adriacin) as asample.

[0036]FIG. 19 shows graphs illustrating the results of performingspectral analysis using nimustine hydrochloride (ACNU) as a sample.

[0037]FIG. 20 is a graph illustrating secondary differential data of theinfrared absorption spectrum of doxorubicin hydrochloride (Adriacin).

[0038]FIG. 21 is a graph illustrating secondary differential data of theinfrared absorption spectrum of nimustine hydrochloride (ACNU).

[0039]FIG. 22 is a graph illustrating secondary differential data of theinfrared absorption spectrum of mouse heart muscle.

[0040]FIG. 23 is a graph illustrating secondary differential data of theinfrared absorption spectrum of mouse striated muscle.

[0041]FIG. 24 is a graph illustrating secondary differential data of theinfrared absorption spectrum of mouse smooth muscle.

[0042]FIG. 25 shows graphs illustrating the results of spectral analysisin the case of using Escherichia coli as a sample.

[0043]FIG. 26 shows graphs illustrating the results of spectral analysisin the case of using aztreonam (Azactam) as a sample.

[0044]FIG. 27 shows graphs illustrating the results of spectral analysisin the case of using transplatin as a sample.

[0045]FIG. 28 is a graph showing the secondary differential data of theinfrared absorption spectrum of lenograstim (Neutrogin).

[0046]FIG. 29 is a graph showing the secondary differential data of theinfrared absorption spectrum of filgrastim (Gran).

[0047]FIG. 30 is a graph showing the secondary differential data of theinfrared absorption spectrum of human bone marrow fluid.

[0048]FIG. 31 is a flow chart showing the disease type and/or conditiondetermination method as described in an embodiment of the presentinvention.

[0049]FIG. 32 is a block diagram showing the configuration of a diseasetype and/or condition diagnostic apparatus as described in an embodimentof the present invention.

[0050]FIG. 33 is a flow chart showing the drug screening method asdescribed in an embodiment of the present invention.

[0051]FIG. 34 is a block diagram showing the configuration of a drugscreening apparatus as described in an embodiment of the presentinvention.

BEST MODE FOR CARRYING OUT THE INVENTION

[0052] To begin with, an explanation is provided of the basic matters ofthe present invention.

[0053] As was previously described, the present invention adopts thestandpoint of employing thermodynamic and statistical mechanical methodsin perceiving a single cell in the form of a macroscopic system andelucidating the absolute specificity of cells and so forth by focusingon the energy state of that system. Thus, in the present invention,cells are considered to be “a thermodynamically unbalanced open system”,and for example, cancer cells and normal cells, etc. can be observed inthe form of differences in the states of that system (quantum intrinsicenergy state).

[0054] Differences in the states of the above cancer cell and normalcell systems can be easily explained by using a model of three-statemaser as shown, for example, in FIG. 1. Here, the three energy statesare represented by Eh, Em and En (the size relationship of the energylevels is Eh>Em>En. It should be noted that the reason for using athree-state maser model is to avoid making the explanation excessivelycomplex, while in actuality, it would be more appropriate to use a modelof a system depicting numerous energy states.

[0055] In the case of FIG. 1, normal cell are in state En, while thosecells that successfully change to state Em (metastable state) afterpassing through state Eh as a result of those normal cells absorbingsuitable energy E₁ are considered to be cancer cells. In addition,contact with a different system having an energy level that is able toresonate with this system is necessary to inductively cause the cancercells to change from metastable state Em to state En or its vicinity.Anti-cancer agents share this energy level and this is thought to be thereason for their selective action against cancer cells.

[0056] The following provides a detailed explanation of the validity ofthe above approach while indicating experimental results. It should benoted that in the following explanation, while the explanation focusesprimarily on the use of analysis of the energy absorption spectrum, thepresent invention can also be carried out by using analysis of theenergy emission spectrum.

[0057] In order for the above approach to acquire validity, it is firstnecessary to confirm the fact that there exists an energy level that isunique and common to a plurality of cancer cells. Therefore, measurementof the infrared absorption spectrum was performed using FT-IR(Fourier-Transform Infrared spectroscopy) and cultured viable cancercells sampled from a specimen for the sample. The FT-IR system is atypical measuring system for analyzing absorption peaks by determiningthe spectrum by irradiating light onto the sample and performing Fouriertransformation on the two-beam interference curve of infrared light thatis transmitted or reflected. For actual measurement, FT-IR systems wereused in which the wave number measurement error is within ±0.1 cm⁻¹(Shimadzu: FTIR8100 and 8300), and sample treatment and measurement wereperformed at room temperature. Furthermore, caution was taken duringmeasurement by FT-IR so that the sample cells were dispersed in themeasured region.

[0058]FIGS. 2 through 7 show examples of the results of performingspectral analysis of various types of cancer cells. In (A) of eachfigure, the infrared absorption spectrum measured by FT-IR is indicatedon the horizontal axis as a wave number (cm⁻¹), while in (B) of eachfigure, the data of (A) is processed by differentiating to the secondorder so as to clarify the wave number of the absorption peaks.

[0059] More specifically, FIG. 2 illustrates data in the case of usingas a sample cultured cells derived from rat ascitic liver cancer(AH7974), FIG. 3 that of cultured cells derived from mouse breast cancer(Ehrlich), FIG. 4 that of cultured cells derived from mouse malignantmelanoma (B16), FIG. 5 that of cultured cells derived from human stomachcancer (HGC27), FIG. 6 that of cultured cells derived from humanglioblastoma (U251), and FIG. 7 that of cancer cells extracted from abreast cancer patient.

[0060] It was found from FIGS. 2 through 7 that a wave number of 1261.4cm⁻¹ exists as a wave number of the infrared absorption spectrum commonto all cancer cells, and that there exists a group of the infraredabsorption spectrum corresponding to at least two wave numbers in eachcancer cell. The former is a fact that was also described in thepreviously mentioned prior publications, and the data indicated hereserves to support this fact. In addition, the former is a fact thatcorrelates with contents that characterize the present invention.

[0061]FIG. 8 is a diagram providing a systematic representation of thepeak wave numbers of the infrared absorption spectra of various cancercells.

[0062]FIG. 8 shows the data resulting from adding 12 types of cancercell samples to each of the samples shown in the above FIGS. 2 through7. More specifically, cultured cells derived from human tongue cancer(SCCKN), cultured cells derived from human colon cancer (C-1), culturedcells derived from human stomach cancer (MKN45), cultured cells derivedfrom mouse breast cancer (MCH66, MCH271), cultured cells derived fromhuman breast cancer (MDA4A4), cultured cells derived from human coloncancer (HT29), and cultured cells derived from human glioblastoma(A-172, U87MG, Becker, SF126, Marcus) were respectively added assamples.

[0063] As shown in FIG. 8, it was found that there was a wave number of1261.4 cm⁻¹ that was common to the characteristic absorption spectrum ofeach type of cancer cell, and there were also characteristic absorptionspectra that were common to not all but some of the cancer cells.Namely, the cancer cells were thought to have absorption spectracorresponding to at least two wave numbers with respect to the infraredregion. Within the range of the measurement results shown, those wavenumbers of infrared absorption spectra that were able to be judged to bespecific for cancer cells consisted of 1261.4 cm⁻¹ as well as 1163.1cm^(−1,) 1168.8 cm^(−1,) 1203.6 cm^(−1,) 1211.3 cm^(−1,) 1224.7 cm^(−1,)1257.5 cm^(−1,) 1290.3 cm⁻¹ and 1319.3 cm⁻¹. It should be noted that theinfrared absorption spectra specific to cancer cells are not limited tothe above wave numbers.

[0064] Moreover, the following provides a detailed explanation of whatis meant by the energy state characteristic of cancer cells as describedabove being a metastable state.

[0065] In order to show that this energy state is a metastable state,measurements were performed here to determine the manner in which theenergy state of the system changes as a result of disturbing the systemwith respect to the cancer cells, namely destroying the cell membrane.

[0066]FIG. 9 shows graphs illustrating changes in energy states causedby destruction of the cell membrane of cancer cells. (A) indicates thesecondary differential data of the infrared absorption spectrum measuredimmediately after destruction, (B) indicates the secondary differentialdata two minutes after destruction, and (C) indicates the secondarydifferential data 5 minutes after destruction.

[0067] As shown in FIG. 9, the absorption spectrum at a wave number of1261.4 cm⁻¹ characteristic of cancer cells rapidly changes to anabsorption spectrum having a wave number of 1259.4 cm⁻¹ due todestruction of the cell membrane. This transition of the absorptionspectrum indicates a change from energy state Em to energy state Em*(Em>Em*), and ultimately ends after reaching a state of Em* alone aftergoing through a state in which both energy states Em and Em* arepresent. The amount of time required to change from energy state Em toenergy state Em* after going through a state of coexistence of bothenergy states is dependent upon the type of cancer cells andenvironmental temperature, and it is generally considered to be about 10to 300 seconds.

[0068] In addition, measurements were also made to determine the mannerin which the energy state of the system changes as a result of heating(43° C.) without destroying the cell membrane with respect to cancercells.

[0069]FIG. 10 shows graphs illustrating changes in energy states causedby heating cancer cells. (A) indicates the secondary differential dataof the infrared absorption spectrum measured before heating, (B)indicates the secondary differential data immediately after heating for30 minutes, and (C) indicates the secondary differential data 30 minutesafter heating.

[0070] As shown in FIG. 10, it was found that the absorption spectrumhaving a wave number of 1261.4 cm⁻¹ changes to a wave number of 1259.4cm⁻¹ due to heating the cancer cells, and that the energy state changesfrom Em to Em*.

[0071] In this manner, based on the fact that the energy state Emcharacteristic of cancer cells changes to another energy state Em* as aresult of changing the energy state of the system by destroying the cellmembrane or heating cancer cells, energy state Em can be considered tobe a metastable state.

[0072] Secondly, it is also necessary to confirm that an energy levelcharacteristic of cancer cells is not present in normal cells.

[0073] In order to confirm the above fact, infrared absorption spectrawere measured using FT-IR in the same manner as in the previous caseusing 30 types of normal cells including rat and mouse normal cells andnormal human bone marrow cells.

[0074]FIGS. 11 through 14 are graphs shown examples of the results ofspectral analysis performed on various types of normal cells. However,(A) in each figure indicates the infrared absorption spectrum asmeasured by FT-IR, while (B) indicates the results of second orderdifferentiation processing of the data of (A).

[0075] More specifically, FIG. 11 indicates data in the case of using asa sample normal rat brain (white matter) cells, FIG. 12 indicates thatof normal rat liver cells, FIG. 13 indicates that of normal mousemammary gland cells, and FIG. 14 indicates that of normal human bonemarrow cells.

[0076] As shown in FIGS. 11 through 14, it is found that a spectrum thatstrictly coincides (within the range of a measuring accuracy of ±0.1cm⁻¹) with the infrared absorption spectrum measured for the cancercells is not present for the normal cells. Thus, it can be judged thatthe previously mentioned wave number of 1261.4 cm⁻¹ and the otherinfrared absorption spectra are specific for cancer cells.

[0077] Furthermore, it was unknown at the time of filing of the presentapplication as to whether or not a common absorption spectrum exists forall normal cells as in the case of cancer cells. FIG. 15 is a diagramproviding a systematic representation of the peak wave numbers of theinfrared absorption spectra for some of the 30 types of normal cellsmeasured.

[0078] Thirdly, it is necessary to confirm that an energy level thatcoincides with the energy level characteristic of cancer cells ispresent in anti-cancer agents.

[0079] In order to confirm the above fact, measurements of infraredabsorption spectra were performed using FT-IR and various types oftypical anti-cancer agents as samples. It should be noted that all ofthe samples used were physiological saline solutions of the pure drugs.

[0080]FIGS. 16 through 19 are graphs illustrating examples of theresults of performing spectral analysis of various anti-cancer agents.However, (A) in each figure indicates the infrared absorption spectrummeasured by FT-IR, while (B) indicates the results of second orderdifferentiation processing of the data of (A).

[0081] More specifically, FIG. 16 indicates the data in the case ofusing cisplatin for the sample, FIG. 17 indicates the use ofcarboplatin, FIG. 18 indicates the use of doxorubicin hydrochloride(drug name: Adriacin, (Kyowa Hakko)), and FIG. 19 indicates the use ofnimustine hydrochloride (ACNU).

[0082] Each of the anti-cancer agents shown in FIGS. 16 through 19 hasan absorption peak at a wave number of 1261.4 cm⁻¹, and this strictlycoincides with the absorption spectrum characteristic of cancer cells.In addition, cisplatin and doxorubicin hydrochloride also have anabsorption spectrum at a wave number of 1163.1 cm⁻¹, while ACNU has anabsorption spectrum at wave numbers of 1203.6 cm⁻¹ and 1211.3 cm⁻¹.These also strictly coincides with the absorption spectrumcharacteristic of cancer cells. Although the specific spectrum analysisresults have been omitted from the graphs, in addition to thosementioned above, anti-cancer agents having an absorption spectrum at awave number of 1163.1 cm⁻¹ included fluorouracil (drug name: 5-FU (KyowaHakko)), methotrexate (MTX) and bleomycin hydrochloride (BLM). Moreover,an absorption spectrum at a wave number of 1261.4 cm⁻¹ was alsoconfirmed for both CBDCA, a variation of cisplatin, and Epi-ADR, avariation of doxorubicin hydrochloride.

[0083] In general, each of the anti-cancer agents shown in FIGS. 16through 19 are anti-cancer agents having powerful killing damagingeffects that are the first choice in cancer chemotherapy. On the otherhand, fluorouracil, methotrexate and bleomycin hydrochloride areanti-cancer agents having comparatively mild action. Thus, it isbelieved that the sharing of an absorption spectrum at a wave number of1261.4 cm⁻¹ with cancer cells is a required condition for being apowerful anti-cancer agent. However, since it is also a fact that thereare numerous cancer cells for which anti-cancer agents having anabsorption spectrum at a wave number of 1261.4 cm⁻¹ are completelyineffective, it is clear that the having of an absorption spectrum at awave number of 1261.4 cm⁻¹ cannot be a sufficient condition for being apowerful anti-cancer agent. This is thought to be because theabove-mentioned cancer cells are allowed to adopt a plurality of statesin addition to the energy state corresponding to an absorption spectrumat a wave number of 1261.4 cm⁻¹.

[0084] Fourthly, it is necessary to confirm that an intrinsic energylevel exists between anti-cancer agents and normal cells damaged byadverse side effects.

[0085] In order to confirm the above fact, an experiment was conductedhere focusing on the myocardial toxicity of, for example, doxorubicinhydrochloride (Adriacin). More specifically, a wave number of 1217.0cm⁻¹ was identified as an infrared absorption spectrum that coincidesbetween doxorubicin hydrochloride and mouse heart muscle. In order forthis absorption spectrum to be the cause of myocardial toxicity, it isnecessary that this absorption spectrum be intrinsic to heart muscle,and that an absorption spectrum at a wave number of 1217.0 cm⁻¹ not bepresent in epirubicin hydrochloride (drug name: Farmorubicin(Farmitalia-Kyowa Hakko)), in which the adverse side effect ofmyocardial toxicity has been removed, or other anti-cancer agents whichdo not inherently possess myocardial toxicity. Therefore, the infraredabsorption spectra were measured using doxorubicin hydrochloride,epirubicin hydrochloride, cisplatin, carboplatin, ACNU, mouse heartmuscle, striated muscle and smooth muscle as samples.

[0086]FIGS. 20 through 24 are graphs showing examples of secondarydifferential data of the infrared absorption spectra measured for eachof the above samples.

[0087] More specifically, FIG. 20 shows the secondary differential datain the case of using doxorubicin hydrochloride for the sample, FIG. 21shows that in the case of using epirubicin hydrochloride, FIG. 22 showsthat in the case of using mouse heart muscle, FIG. 23 shows that in thecase of using mouse striated muscle, and FIG. 24 shows that in the caseof using smooth muscle.

[0088] As shown in FIGS. 20 through 24, the absorption spectrum at awave number of 1217.0 cm⁻¹ is clearly a spectrum intrinsic only todoxorubicin hydrochloride and heart muscle, and the above findings werestrictly confirmed experimentally.

[0089] As a result of being able to confirm the first to fourth factsdescribed above, it can be judged that it is reasonable to think thatabsolute specificity regarding cancer cells or anti-cancer agentsrelative to normal cells is observed in the form of differences in theenergy states of the systems.

[0090] The explanation thus far has focused on the specificity possessedby cancer cells and anti-cancer agents, and the above approach can besimilarly applied to bacteria and antibiotics as well as to viruses andanti-viral agents. This is because ordinary cells, including cells thathave been infected by bacteria and viruses, are an open system that isin a state of thermal imbalance with respect to their survival, and thenormal state (energy state En shown in the above FIG. 1) is also notconsidered to be a basal state, but rather an unstable excited state,namely a metastable state. This is clear from the fact that thesituation in which normal cells require a supply of energy from theoutside in order to demonstrate biological activity is not differentfrom that of cancer cells.

[0091] In order to confirm the above contents experimentally,measurement of infrared absorption spectrum was performed by FT-IR usingEscherichia coli and aztreonam (drug name: Azactam, Eisai), which isknown to be an effective antibiotic against it, as samples.

[0092]FIG. 25 shows graphs illustrating the results of infrared spectralanalysis in the case of using Escherichia coli as a sample, while FIG.26 shows graphs illustrating the results of spectral analysis in thecase of using aztreonam (Azactam) as a sample. However, (A) in eachfigure indicates the infrared absorption spectrum measured by FT-IR,while (B) indicates the results of second order differentiationprocessing of the data of (A).

[0093] As shown in FIGS. 25 and 26, an absorption peak at a wave numberof 1259.4 cm⁻¹ was identified as an infrared absorption spectrum commonto Escherichia coli and aztreonam. Moreover, this absorption spectrumhaving a wave number of 1259.4 cm⁻¹ is also present in cisplatin (FIG.16) and carboplatin (FIG. 17) previously mentioned as anti-canceragents. This can be considered to suggest the possibility that cisplatinand carboplatin also have the ability to impair Escherichia coli.

[0094] In addition, the infrared absorption spectrum was also measuredfor transplatin, a coordination isomer of cisplatin.

[0095]FIG. 27 shows graphs illustrating the results of spectral analysisin the case of using transplatin as a sample, and (A) indicates themeasured infrared absorption spectrum, while (B) indicates the secondarydifferential data.

[0096] As shown in FIG. 27, although transplatin has an absorptionspectrum at a wave number of 1259.4 cm⁻¹ that is common to Escherichiacoil, it can be seen that there are no spectra that coincide with thecharacteristic absorption spectrum of cancer cells. This is believed tosuggest the possibility that even though transplatin is a coordinationisomer of cisplatin, it has the ability to impair Escherichia coli butdoes not have the ability to impair cancer cells.

[0097] Moreover, an attempt was also made to measure the infraredabsorption spectra for samples consisting of the drug resistancebacteria, methicillin-resistant Staphylococcus aureus (MRSA),Staphylococcus aureus (SA), the origin of the MRSA, and vancomycin (VM),an antibiotic that is effective against both MRSA and Staphylococcusaureus.

[0098] The following Table 1 shows the absorption peak wave numbers ofthe infrared absorption spectra measured for each of these samples.TABLE 1 MRSA S.A. V.M. 1006.8 1006.8 1010.6 1014.4 1022.2 1022.2 1018.31033.8 1033.8 1029.9 1041.5 1037.6 1056.9 1056.9 1064.6 1076.2 1076.21083.9 1083.9 1080.1 1087.8 1087.8 1118.6 1118.6 1130.2 1172.6 1172.61176.5 1195.8 1195.8 1218.9 1218.9 1234.4 1234.4 1242.1 1242.1 1245.91245.9 1265.2 1265.2 1280.7 1280.7 1296.1 1296.1 1303.8 1303.8 1311.5

[0099] As shown in Table 1, absorption spectra were confirmed tocoincide between MRSA and vancomycin at wave numbers of 1076.2 cm⁻¹,1195.8 cm⁻¹, 1234.4 cm⁻¹ and 1265.2 cm⁻¹. In addition, an absorptionspectrum at a wave number of 1296.1 cm⁻¹ was confirmed to coincidebetween Staphylococcus aureus and vancomycin.

[0100] In this manner, the approach of observing the absolutespecificity of cells as differences in the energy state of the systemcan be judged to be valid even when applying to bacteria such asEscherichia coli, MRSA and Staphylococcus aureus as well as antibioticsthat act on said bacteria.

[0101] In addition, although the experimental results shown thus farhave focused on drugs that impair cancer cells and Escherichia coli, thefact has also been confirmed that coincidence between the infraredabsorption spectra of cells and drugs activates cell growth.

[0102] Here, the infrared absorption spectra were measured for samplesconsisting of, for example, lenograstim (drug name: Neutrogin, ChugaiPharmaceutical), filgrastim (drug name: Gran, Sankyo) and normal humanbone marrow cells. Furthermore, lenograstim and filgrastim are bothdrugs that increase leukocytes and are used during bone marrowtransplants, with lenograstim being a drug that is extracted from theovaries of Chinese hamsters, and filgrastim being a drug that issynthesized in Escherichia coli that has a different molecular structurethan lenograstim.

[0103]FIGS. 28 through 30 show the secondary differential data of theinfrared absorption spectra measured for each of the above samples, withFIG. 28 showing the data for lenograstim, FIG. 29 showing that forfilgrastim, and FIG. 30 showing that for bone marrow fluid.

[0104] As shown in FIGS. 28 through 30, the absorption spectra oflenograstim, filgrastim and bone marrow fluid can be seen to strictlycoincide at a wave number of 1328.9 cm⁻¹. In this manner, coincidencebetween the absorption spectra of cells and drugs is thought to beeffective with respect to the case of activation of cell growth as well.

[0105] Next, in order to experimentally confirm that the approach of thepresent invention can also be applied to viruses and anti-viral agents,the infrared absorption spectra were measured by FT-IR for samplesconsisting of, for example, KOS virus, which is a type of herpes virusthat has drug sensitivity, and aciclovir (drug name: Zovirax,Sumitomo-Welcam Japan), which is known to be an effective anti-viralagent against the KOS virus.

[0106] Here, fibroblasts (VERO cells) and kidney cells of rhesus monkeys(MRC5 cells) were used as cells infected with the above KOS virus and inwhich the KOS virus was allowed to grow. The infrared absorption spectrawere then measured for each of the sample cells before viral infectionand 1, 3 and 5 days after infection. In addition, the infraredabsorption spectrum of the anti-viral agent aciclovir was also measured.

[0107] The following Table 2 shows the absorption peak wave numbers ofthe infrared absorption spectra measured for each sample. TABLE 2 VERO(cm⁻¹) MRC5 (cm⁻¹) One day Three Five days One day Three Five daysBefore after days after after Before after days after after Aciclovirinfection infection infection infection infection infection infectioninfection (cm⁻¹) 1010.6 1016.4 1016.4 1016.4 1022.2 1022.2 1029.9 1037.61037.6 1037.6 1041.5 1041.5 1047.3 1049.2 1049.2 1049.2 1049.2 1051.11051.1 1055.0 1055.0 1055.0 1058.8 1058.8 1058.8 1058.8 1064.6 1064.61064.6 1064.6 1068.5 1068.5 1068.5 1071.4 1083.0 1087.8 1087.8 1087.81087.8 1091.6 1103.2 1103.2 1103.2 1105.1 1105.1 1105.1 1105.1 1105.11107.1 1107.1 1107.1 1107.1 1117.7 1122.5 1122.5 1122.5 1122.5 1157.21157.2 1157.2 1161.1 1161.1 1176.5 1176.5 1176.5 1179.4 1182.3 1182.31182.3 1182.3 1193.9 1193.9 1193.9 1193.9 1195.8 1195.8 1195.8 1195.81201.6 1201.6 1207.4 1207.4 1207.4 1209.3 1209.3 1209.3 1213.1 1230.51230.5 1232.4 1232.4 1232.4 1233.4 1240.1 1240.1 1240.1 1240.1 1245.01251.7 1251.7 1259.4 1259.4 1259.4 1259.4 1259.4 1265.2 1269.1 1269.11269.1 1269.1 1274.9 1274.9 1274.9 1276.8 1278.7 1278.7 1278.7 1286.4

[0108] As shown in Table 2, there were numerous absorption spectra thatappeared after viral infection but not before infection for each of thesample cells. In addition, there were also absorption spectra that werepresent before infection but disappeared after infection. Morespecifically, examples of spectra that disappeared after infection forboth sample cells included those at wave numbers of 1037.6 cm⁻¹, 1055.0cm⁻¹, 1068.5 cm⁻¹, 1103.2 cm⁻¹, 1209.3 cm⁻¹, 1232.4 cm⁻¹ and 1274.9cm⁻¹. The above fact is believed to indicate that the energy state ofcells changes as a result of those cells being infected by virus. Thischange in the cell energy state is also clear from the fact that theinfected cells begin virus replication and eventually die. In addition,absorption spectra were able to be confirmed to coincide betweenabsorption spectra that newly appeared after viral infection and theabsorption spectrum of the anti-viral agent aciclovir for each of thesample cells at wave numbers of 1105.1 cm⁻¹ and 1122.5 cm⁻¹.

[0109] In this manner, the approach of observing the absolutespecificity of cells as difference in the energy state of the system canbe judged to also have validity with respect to application to virusesand anti-viral agents.

[0110] As a result of employing the basic approach of the presentinvention as described above, a disease type and/or conditiondetermination method and apparatus, which enable rapid and accuratedetermination of condition, as well as a drug screening method andapparatus, which enables efficient screening of drugs, can be realizedas indicated below.

[0111] To begin with, an explanation is provided regarding an embodimentof the disease type and/or condition determination method according tothe present invention.

[0112]FIG. 31 is a flow chart showing the disease type and/or conditiondetermination method as described in an embodiment of the presentinvention.

[0113] As shown in FIG. 31, in the method of the present embodiment,viable cells are sampled from a specimen in step 101 (indicated as S101in the figure, and to apply similarly hereinafter), and those cells arethen used as a sample.

[0114] It should be noted that the specimen from which cells are sampledis not limited to a human, but also applies to a wide range of animalsand plants. This is also clear from the experimental data previouslydescribed. In addition, the sampled samples may also be cultured and soforth. Moreover, caution is required so that the cells used as a sampledo not cause a change in the energy state of the system as a result ofdestruction of the cell membrane or heating as previously mentioned.More specifically, the sample cells are preferably handled in alow-temperature state.

[0115] In step 102, measurement of absorption spectrum is performed inthe infrared region by, for example, FT-IR for the viable cells sampledin step 101. Since this measurement is performed in an extremely shortperiod of time, the energy state of the cells can be monitored while thecells are still viable without causing the cells to die.

[0116] Next, in step 103, disease type or condition is determined usingas an index the appearance of spectra corresponding to at least two wavenumbers within the infrared region for the infrared absorption spectrummeasured in step 102.

[0117] More specifically, in the case cancer is suspected in thespecimen, whether or not cancer is present is judged according towhether or not coinciding absorption spectra are present in measurementresults by using as an index a plurality of infrared absorption spectracharacteristic of cancer cells identified in advance. For the infraredabsorption spectra characteristic of cancer cells, that at a wave numberof 1261.4 cm⁻¹ is essential as previously mentioned, while at least onewave number among 1163.1 cm⁻¹, 1168.8 cm⁻¹, 1203.6 cm⁻¹, 1211.3 cm⁻¹,1224.7 cm⁻¹, 1257.5 cm⁻¹, 1290.3 cm⁻¹ and 1319.3 cm⁻¹ should also beused as indices (see FIG. 8). In the case an absorption spectrum thatcoincides with these wave numbers is present in the measurement results,then that specimen is determined to be cancer.

[0118] In addition, in the case a specimen is suspected of beinginfected by, for example, MRSA, the infected state of the specimen isdiagnosed by determining whether or not a coinciding absorption spectrumis present in the measurement results using as indices infraredabsorption spectra having any of the above wave numbers of 1076.2 cm⁻¹,1195.8 cm⁻¹, 1234.4 cm⁻¹ and 1265.2 cm⁻¹ and so forth.

[0119] Moreover, in the case a specimen is suspected of being infectedby, for example, KOS virus, the infected state of the specimen isdiagnosed by determining whether or not a coinciding absorption spectrumis present in the measurement results using as indices infraredabsorption spectra having any of the above wave numbers of 1105.1 cm⁻¹and 1122.5 cm⁻¹ and so forth.

[0120] It should be noted that although the explanation here has focusedon the use of FT-IR having a measuring accuracy of ±0.1 cm⁻¹, even incases of more inferior measuring accuracy, it is still possible todetermine disease type and condition, and more specifically, it isthought that a measuring accuracy of about ±1 cm⁻¹ should be obtained.Thus, the above values to the right of the decimal point of wave numbersof the absorption spectra used as indices may be rounded up or down asis appropriate. Naturally, it is also possible to use FT-IR havingsuperior measuring accuracy of ±0.1 cm⁻¹, and in this case, absorptionspectra within the ranges included in the above values should be used asindices.

[0121] In addition, as an example of a method for determining theinfrared absorption spectra of at least two wave numbers used as indicesin order to confirm the presence of a specific bacterium such as MRSA orthe presence of a specific virus such as KOS virus, the energy spectramay be analyzed for a specific bacterium or virus and a plurality ofother bacteria or viruses followed by determining the presence of thatbacterium or virus by identifying specific absorption spectra present inthat specific bacterium or virus only.

[0122] In this manner, according to the disease type and/or conditiondetermination method of the present embodiment, by employing a simplemethod involving analyzing the energy spectrum for viable cells obtainedfrom a specimen, the disease type or conditions can be rapidlydetermined such as whether or not the cells are cancer cells and whetheror not the cells are infected by MRSA or KOS virus. In addition, byjudging and processing spectral measurement results using as indices theabsorption spectra corresponding to a plurality of wave numbers withinthe infrared region, determination of disease type and so forth can beperformed more reliably.

[0123] Next, an explanation is provided of an embodiment of a diseasetype and/or condition diagnostic apparatus according to the presentinvention.

[0124]FIG. 32 is a block diagram showing the configuration of a diseasetype and/or condition diagnostic apparatus as described in the presentembodiment.

[0125] In FIG. 32, the present apparatus 1 is composed of spectralmeasuring instrument 10, which is used as spectral analysis means thatperforms analysis of absorption or emission spectra for cells obtainedfrom a specimen, and a diagnostic processing unit 11, which is used asdiagnostic means that diagnoses disease type and/or condition based onthe measurement results of the spectral measuring instrument 10. Here,an FT-IR system and so forth is used for a spectral measuring instrument10 that measures absorption spectra for the infrared region. Inaddition, data relating to infrared absorption spectra used as indicesto diagnose disease type and so forth is preset in the diagnosticprocessing unit 11.

[0126] In diagnostic apparatus 1 having the above configuration, viablecells sampled from a specimen are used as a sample, infrared absorptionspectrum is measured by the spectral measuring instrument 10, and thosemeasurement results are sent to the diagnostic processing unit 11. Inthe diagnostic processing unit 11, disease type and condition arediagnosed using as indices the appearance of spectra corresponding to atleast two wave numbers in the infrared region for the infraredabsorption spectrum measured with the spectral measuring instrument 10in the same manner as the above-mentioned step 103.

[0127] Thus, according to the present embodiment, a diagnostic apparatuscan be realized with a simple apparatus configuration that allows rapidand accurate diagnosis of disease type and condition.

[0128] It should be noted that although the explanation of each of theabove embodiments focused on determining whether or not a specimen has adisease, the present invention is not limited to this application, butis also able to determine the degree of the progress of a disease. As aspecific example of this, since the infrared absorption spectrumspecific for cancer cells is thought to change depending on metastasisof the cancer and so forth, if spectral wave numbers used as indices aresuitably set by correlating with the site of the cancer and so forth,and spectral analysis is performed on extracted cells, then the degreeof the progress of that cancer can be determined. In addition, this canalso be applied similarly to bacterial and viral infections.

[0129] Next, an explanation is provided of an embodiment of the drugscreening method according to the present invention.

[0130]FIG. 33 is a flow chart showing the drug screening method asdescribed in the present embodiment.

[0131] In the drug development method shown in FIG. 33, the absorptionspectrum in the infrared region is measured using, for example, FT-IRfor a new drug or existing drug for which new action (including adverseside effects) is expected (target drug) in step 201.

[0132] Next, in step 202, the target drug is screened using as indicesthe appearance of spectra corresponding to at least two wave numbers inthe infrared region for the infrared absorption spectrum measured instep 201.

[0133] More specifically, in the case the target drug is, for example,an anti-cancer agent, screening is performed on the condition that thereis at least one coinciding absorption spectrum in the spectralmeasurement results of the target drug among the plurality of infraredabsorption spectrum used as indices at wave numbers of 1261.4 cm⁻¹,1163.1 cm⁻¹ and so forth as previously mentioned. Moreover, if ananti-cancer agent is to be selected that does not have the adverse sideeffect of myocardial toxicity, for example, screening should beperformed on the condition that an absorption spectrum does not exist inthe measurement results for the target drug that coincides with theabsorption spectrum at a wave number of 1217.0 cm⁻¹ used as the index.

[0134] In addition, in the case of the target drug being, for example,an antibiotic effective against MRSA, screening should be performed onthe condition that there is at least one coinciding absorption spectrumpresent in the spectral measurement results of the target drug amonginfrared absorption spectra used as indices at the above-mentioned wavenumbers of 1076.2 cm⁻¹, 1195.8 cm⁻¹, 1234.4 cm⁻¹ and 1265.2 cm⁻¹ and soforth. Moreover, in the case of the target drug being, for example, anantibiotic effective against Escherichia coli, screening may beperformed using as the index the infrared absorption spectrum at a wavenumber of 1259.4 cm⁻¹.

[0135] Moreover, in the case of the target drug being, for example, ananti-viral agent effective against KOS virus, screening should beperformed on the condition that at least one coinciding absorptionspectrum is present in the spectral measurement results of the targetdrug among infrared absorption spectra used as indices at theabove-mentioned mentioned wave numbers of 1105.1 and 1122.5 cm⁻¹ and soforth.

[0136] Furthermore, the absorption spectra used as indices for anantibiotic effective against MRSA are not limited to those indicatedabove. The above values were merely confirmed as a result of measuringby using vancomycin as the sample, and there is a strong possibilitythat other absorption spectra exist that are characteristic of MRSA. Anantibiotic more effective than vancomycin can be expected to bedeveloped if other absorption spectra characteristic of MRSA can beidentified. In addition, this applies similarly to an antibioticeffective against Escherichia coli and an anti-viral agent effectiveagainst KOS virus.

[0137] In addition, although the explanation here as well has focused onthe use of FT-IR having a measuring accuracy of ±0.1 cm⁻¹, even in casesof more inferior measuring accuracy, it is still possible to performdrug screening. More specifically, a measuring accuracy of about ±1 cm⁻¹should be obtained, and the above values to the right of the decimalpoint of wave numbers of the absorption spectra used as indices may berounded up or down as is appropriate. Naturally, it is also possible touse FT-IR having superior measuring accuracy of ±0.1 cm⁻¹, and in thiscase, absorption spectra within the ranges included in the above valuesshould be used as indices.

[0138] Thus, according to the drug screening method of the presentembodiment, by using a simple method involving performing spectralanalysis for a target drug, the target drug can be efficiently screenedas to whether or not it is effective against cancer cells, bacteria orviruses, and by judging and processing spectral measurement results of atarget drug using as indices the infrared absorption spectracorresponding to a plurality of wave numbers, this method is consideredto be effective for primary screening and so forth in drug developmentin particular. As a result, both the time and cost required for drugdevelopment can be significantly reduced. Moreover, the present methodis extremely effective in the case of eliminating adverse side effectsfrom existing drugs. Namely, although the adverse side effects of a drugmay be either inherent or not inherent to the drug's action, and it wasdifficult to find that difference with conventional drug developmenttechniques, according to the present method, by identifying the energyspectrum specific to that adverse side effect in the manner of themyocardial toxicity previously described, it becomes easy to judgewhether or not that adverse side effect is inherent to the action of thedrug. Consequently, the time and cost required for developing drugs freeof adverse side effects can be significantly reduced.

[0139] Next, an explanation is provided of an embodiment of the drugscreening apparatus according to the present invention.

[0140]FIG. 34 is a block diagram showing the configuration of a drugscreening apparatus as described in the present embodiment.

[0141] In FIG. 34, the present apparatus 2 is composed of spectralmeasuring instrument 20, which is used as spectral analysis means thatperforms analysis of absorption or emission spectra for a target drug,and a screening processing unit 21, which is used as screening meansthat screens a target drug based on the measurement results of thespectral measuring instrument 20. Here, an FT-IR system and so forth isused for the spectral measuring instrument 20 that measures absorptionspectra for the infrared region. In addition, data relating to infraredabsorption spectra used as indices for drug screening is preset in thescreening processing unit 21.

[0142] In the screening apparatus 2 having the above configuration,infrared absorption spectrum is measured for a target drug by thespectral measuring instrument 20, and those measurement results are sentto the screening processing unit 21. In the screening processing unit21, drug screening is performed using as indices the appearance ofspectra corresponding to at least two wave numbers in the infraredregion for the infrared absorption spectrum measured with the spectralmeasuring instrument 20 in the same manner as the above-mentioned step202.

[0143] According to the present embodiment, a screening apparatus havinga simple configuration can be realized that is able to efficientlyscreen target drugs.

[0144] In each of the above embodiments, although the explanationsfocused on the use of the infrared region as the specific region forperforming analysis of energy spectra. It should be noted, however, thatthe present invention is not limited to use of the infrared region.Since the energy state of a cell system and so forth is expected toextend from the ultraviolet region to the microwave region in the formof molecular transitions, molecular vibrations and rotational energy, itis considered to be quite possible to apply the present invention tothese regions as well.

[0145] In addition, although the case of measuring the absorptionspectrum of a cell system and so forth has been indicated, attention maybe focused on the emission spectrum of a system, and the presentinvention can also be applied in this case as well in the same manner asthe case of the absorption spectrum.

Industrial Applicability

[0146] The present invention has considerable industrial applicabilityas a measuring and testing method for rapidly and reliably determiningdisease type and condition, and as the respective apparatuses forperforming that measuring and testing. In addition, the presentinvention also has considerable industrial applicability as a method forrapidly and reliable screening various drugs, and as the respectiveapparatuses for performing that screening.

1. A disease type and/or condition determination method comprising:analyzing the absorption or emission spectrum in a specific region forcells obtained from a specimen, and determining the disease type and/orcondition by using as indices the appearance of spectra corresponding toat least two wave numbers within said specific region in accordance withthe results of said spectral analysis.
 2. The disease type and/orcondition determination method according to claim 1, wherein saidspecific region includes the infrared region.
 3. The disease type and/orcondition determination method according to claim 1 or 2 that determineswhether or not said specimen is cancer.
 4. The disease type and/orcondition determination method according to claim 3, wherein one of thewave numbers of the spectra used as said indices is 1261 cm⁻¹.
 5. Thedisease type and/or condition determination method according to claim 1or 2 that determines whether or not said cells have specific bacteria.6. The disease type and/or condition determination method according toclaim 5, wherein said specific bacteria are drug resistance bacteria. 7.The disease type and/or condition determination method according toclaim 1 or 2 that determines whether or not said cells are infected by aspecific virus.
 8. A disease type and/or condition diagnostic apparatuscomprising: spectral analysis means that analyzes the absorption oremission spectrum in a specific region for cells obtained from aspecimen, and diagnostic means that diagnoses disease type and/orcondition using as indices the appearance of spectra corresponding to atleast two wave numbers within said specific region in accordance withthe results of the spectral analysis obtained with said spectralanalysis means.
 9. A drug screening method comprising: analyzing theabsorption or emission spectrum in a specific region for a target drug,and screening said target drug by using as indices the appearance ofspectra corresponding to at least two wave numbers within said specificregion in accordance with the results of said spectral analysis.
 10. Thedrug screening method according to claim 9, wherein said specific regionincludes the infrared region.
 11. The drug screening method according toeither of claim 9 or 10, wherein said target drug is an anti-canceragent.
 12. The drug screening method according to claim 11, wherein oneof the wave numbers of the spectra used as said indices is 1261 cm⁻¹ or1163 cm⁻¹.
 13. The drug screening method according to claim 9 or 10,wherein said target drug is an antibiotic.
 14. The drug screening methodaccording to claim 13, wherein said antibiotic is effective against drugresistance bacteria.
 15. The drug screening method according to claim 9or 10, wherein said target drug is an anti-viral agent.
 16. A drugscreening apparatus comprising: spectral analysis means that analyzesthe absorption or emission spectrum in a specific region for a targetdrug, and screening means that screens said target drug using as indicesthe appearance of spectra corresponding to at least two wave numberswithin said specific region in accordance with the results of thespectral analysis obtained with said spectral analysis means.